[Case of chronic renal failure with sudden progression of renal dysfunction due to furosemide hypersensitivity].
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Biomedical subjects
Publications and source records attributed to A Suzuki.
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Firefly luciferase emits a burst of light when the substrates luciferin and ATP are mixed in the presence of oxygen. We (I. Ueda, A. Suzuki, Biophys. J. 75 (1998) 1052-1057) reported that long-chain fatty acids are specific inhibitors of firefly luciferase in competition with luciferin in microM ranges. They increased the thermal transition temperature. In contrast, 1-alkanols of the same carbon chain length inhibited the enzyme non-competitively in mM ranges and decreased the transition temperature. The present study showed that the action of fatty acids switched from specific to non-specific when the carbon chain length was reduced below C8 (octanoate). The fatty acids longer than C10 inhibited the enzyme in microM ranges whereas those shorter than C8 required mM ranges to inhibit it. The longer fatty acids increased whereas shorter fatty acids decreased the transition temperature. The Hill coefficients of longer chain bindings were less than one whereas those of shorter chain were more than one. The shorter fatty acids interacted with the enzyme cooperatively at multiple sites. Binding of the longer fatty acids is limited. Fatty acids longer than C10 are high-affinity specific binders and followed Koshland's induced-fit model. Those shorter than C8 are low-affinity non-specific denaturants and followed Eyring's rate process model. These results contradict the general consensus that the size of the receptor cavity discriminates specific binders.
Phospholipase D (E.C. 3.1.4.4) from Streptomyces antibioticus has been crystallized in six crystal forms using the hanging-drop vapour-diffusion method. The type III and V crystals belong to monoclinic and hexagonal systems, respectively. All of the other crystal forms, types I, II, IV and VI, belong to orthorhombic space group P212121. Of these four types, the type VI crystals are suitable for X-ray structure determination. Crystal data for type VI crystals are: a = 50.1, b = 98.7, c = 107.6 A, V = 532100 A3, Z = 4 and Vm = 2.47 A3 Da-1. Type VI crystals diffract to at least 2.3 A resolution. A total of 11295 independent reflections to 3 A resolution have been collected from a type VI crystal using a conventional X-ray source, and its structural analysis is currently being conducted using isomorphous replacement methods.
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A rapid and sensitive analytical method based on column-switching semi-microcolumn high-performance liquid chromatography (HPLC) with electrospray mass spectrometry was developed for determining trace levels of bisphenol A (2,2-bis(4-hydroxyphenyl)propane) and nonylphenol (4-nonylphenol) in river water. An aliquot of sample solution was directly injected into the precolumn packed with Capcellpak MF-Ph for sample cleanup and enrichment. The compounds of interest were then transferred to a C-18 analytical column for main separation through a change in flow path by a programmed switching valve. Bisphenol A, nonylphenol, and interfering substances were satisfactorily separated with a simple gradient elution complete within 35 min. Detection of their deprotonated molecules was conducted in negative ion mode. A reduced flow rate (100 &mgr;L/min) optimized for the narrow bore column was found advantageous in obtaining a high degree of sensitivity during electrospray detection. The influence of carrier additives on sensitivity was also examined. This method produced detection limits of 0.5 ng/mL for bisphenol A and 10 ng/mL for nonylphenol (signal-to-noise ratio 3). Calibration curves were observed in the range of 2.5-50 ng/mL (r(2) = 0.999) for bisphenol A and 50-500 ng/mL (r(2) = 0.998) for nonylphenol. Recoveries of the compounds from spiked distilled water and river water were 99.7-138.5% with a relative standard deviation (RSD) ranging from 2.2-9.7%. Copyright 1999 John Wiley & Sons, Ltd.
Acquisition of fertilizability in Xenopus coelomic eggs is correlated with the conversion from coelomic to vitelline envelope during passage of the eggs through the pars recta portion of oviduct. The conversion includes processing of a major envelope constituent gp43 of coelomic envelopes to gp41 of vitelline envelopes by a trypsin-type protease, oviductin, which is secreted from the pars recta. Our recent sequencing analyses [Kubo et al., (1997): Dev Growth Diff 39:405-411] strongly suggested that the N-terminal portion of gp41 is exposed as a result of oviductin digestion. In this study, a monoclonal antibody specific to the predicted N-terminus of gp41 was raised by immunizing mice with a synthetic N-terminal hexapeptide (QLPVSP) coupled to keyhole limpet hemocyanin. The antibody specifically reacted to gp41, but not to gp43, indicating that Gln62 is exposed as the N-terminal amino acid of gp41 by oviductin-mediated cleavage of gp43 at Arg61 in GSR61. The C-terminal sequencing of gp43 and gp41 indicated that Arg373 in GSR373 as the C-terminus of gp41 is generated by cleavage of three amino acid (WNQ) residues from the C-terminus of gp43. The resulting polypeptide moiety of gp41 has a molecular mass of 33900 Da with 312 amino acid residues. We propose that oviductin possessing the substrate specificity of GSR simultaneously digests gp43 at Arg residues in GSR61 and GSR373 to generate the N- and C-terminus of gp41, respectively.
PURPOSE: To present a case of rhabdomyolysis which developed in a child with a known history of Duchenne's muscular dystrophy, following an anesthetic which included sevoflurane. CLINICAL FEATURES: An 11 yr old boy with a known history of Duchenne's muscular dystrophy underwent anesthesia for strabismus repair. The anesthetic consisted of sevoflurane and nitrous oxide without the use of a muscle relaxant. His postoperative course was complicated by a complaint of heel pain and the development of myoglobinuria. He was treated with dantrolene sodium and discharged home after two days, without further complication. CONCLUSION: Sevoflurane anesthesia has not been shown previously to be associated with the development of acute rhabdomyolysis in a child with a history of Duchenne's muscular dystrophy. As with halothane and isoflurane, the continued use of sevoflurane in the presence of Duchenne's muscular dystrophy should be questioned.
OBJECTIVE: The plasma volume of histamine-induced protein capillary leakage may be overestimated when this is determined using the indocyanine green (ICG) dilution method (Vd-ICG), since this dye binds to plasma proteins. The initial distribution volume of glucose (IDVG) has been shown to indicate the central extracellular fluid volume including plasma. Accordingly, the overestimation would be detected by a higher Vd-ICG/IDVG ratio. Our study was intended to examine whether the simultaneous measurement of these two variables can evaluate histamine-induced protein leakage and associated hypovolaemia. DESIGN: Prospective animal study. SETTING: Institutional animal research laboratory. SUBJECTS: Twenty-four anaesthetized and ventilated mongrel dogs. INTERVENTIONS: Anaesthetized animals were mechanically ventilated and received infusions of normal saline (n = 8), histamine 50 microg/kg per h (n = 8), or histamine 100 microg/kg per h. The Vd-ICG and IDVG were calculated using a one-compartment model by simultaneous administration of ICG 0.5 mg/kg, and glucose 100 mg/kg followed by serial arterial blood sampling. MEASUREMENTS AND RESULTS: In both histamine groups, a significant elevation of haematocrit and a decrease of plasma albumin concentration were found (p<0.05). Although the IDVG decreased following histamine administration (p<0.05), the Vd-ICG remained unchanged. The Vd-ICG/IDVG ratio increased in a dose-dependent manner after histamine administration (p<0.05), but remained unchanged following normal saline administration. CONCLUSION: The results suggest that the Vd-ICG/IDVG ratio and the IDVG are useful in evaluating the magnitude of the leakage and hypovolaemia.
Our aim was to study the relationship between cerebral blood flow (CBF) responses to induced hypotension and to CO2 inhalation in patients with occlusive disease of the carotid or middle cerebral arteries. In 13 patients (8 men, 5 women) aged 31-73 years (mean +/- 1 SD = 63.2 +/- 10.6), regional CBF values during the resting state (CBFrest), 7% CO2 inhalation (CBFhypercapnia), and hypotension induced by 10-20 microg/kg/min intravenous trimethaphan (CBFhypotension) were measured using positron-emission tomography (PET) with H2(15)O. The % CBF change during induced hypotension (% CBFhypotension) was defined as (CBFhypotension - CBFrest)/CBFrest multiplied by 100. The % CBF change during CO2 inhalation (% CBFhypercapnia) was defined as (CBFhypercapnia - CBFrest)/CBFrest/mm Hg arterial partial pressure of CO2 x 100. We defined symptomatic hemispheres as those with a stenotic or occlusive lesion with neurological symptoms or signs and asymptomatic hemispheres as those which had a similar lesion and/or were influenced by the collateral flow pattern without neurological symptoms. In the territory of the occlusive lesion, % CBFhypotension correlated significantly with % CBFhypercapnia (r = 0.793, P < 0.002) in the symptomatic hemispheres. In the brain regions in which trimethaphan did not induce a reduction in CBF. % CBFhypercapnia was 6.13 +/- 1.79. In those in which % CBFhypotension ranged from 0 to -5, from -5 to -10, and more than -10%, % CBFhypercapnia was 4.05 +/- 1.99, 3.21 +/- 1.17, and 1.73 +/- 1.61, respectively, with significant differences between each pair of groups. In the asymptomatic hemispheres, % CBFhypotension also correlated with % CBFhypercapnia (r = 0.979, P < 0.0001). Failure to maintain CBF during induced hypotension was associated with diminished cerebrovascular vasoreactivity to hypercapnia in patients with arterial disease. This may indicate that failure of autoregulation can be assessed by the CBF response to both induced hypotension and CO2 inhalation. From the technical point of view, estimation of the CO2 response may be useful for assessing failure of autoregulation.
Analysis of reports about incidental and accidental events in nursing care were made using a reliability engineering method. Unnatural working hours, such as evening duty, night duty falling next to a holiday, two consecutive night-duty shifts, and two consecutive evening-duty shifts were major factors in the occurrence of errors. In a mixed-division ward (a ward containing patients belonging to different divisions), rule-based errors happened more frequently than in a single-division ward. Also, less experienced nursing staffs made errors more frequently than experienced nursing staffs.
BACKGROUND: The CYP2D6*10 (*10) allele that causes decreased CYP2D6 activity is present in Asians with a high frequency of about 50%. In this study we studied the effects of the *10 allele on the steady-state plasma concentrations (Css) of haloperidol and reduced haloperidol. METHODS: The subjects were 67 Japanese inpatients with schizophrenia who had only the wild-type or *10 alleles. Thirty-four patients were homozygous for the wild-type allele, and 26 were heterozygous and 7 were homozygous for the *10 allele. All patients had been receiving 12 mg/day haloperidol for at least 2 weeks. Plasma concentrations of haloperidol and reduced haloperidol were measured by HPLC. RESULTS: The mean +/- SD values of haloperidol Css in the patients with 0, 1, and 2 *10 alleles were 22.8+/-11.0, 30.1+/-10.6, and 31.2+/-21.2 nmol/L, respectively, and those values for reduced haloperidol were 6.1+/-2.9, 9.5+/-3.7, and 9.9+/-6.2 nmol/L, respectively. The mean haloperidol Css was significantly (P < .05) higher in the patients with 1 *10 allele than in those with no *10 alleles. The mean Css of reduced haloperidol was significantly (P < .05) higher in the patients with 1 and 2 *10 alleles than in those with no *10 alleles. CONCLUSION: This study suggests that the *10 allele plays an important role in controlling the Css of both haloperidol and reduced haloperidol, especially in Asian subjects.
BACKGROUND & AIMS: Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs. METHODS: Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories). RESULTS: With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P < 0.05), but more fat was absorbed with porcine lipase (P < 0.05); 600, 000 IU of bacterial lipase (240 mg) and 300,000 IU of porcine lipase (18 g) nearly abolished steatorrhea. With 300,000 IU of bacterial lipase or 135,000 IU of porcine lipase, fat absorption was greater with the high-fat and -protein diet (P < 0.05 vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption. CONCLUSIONS: Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.
BACKGROUND: Spinal artery aneurysms are rare, and are usually found in association with arteriovenous malformations or coarctation of the aorta. CASE REPORT: A 42-year-old man with a ruptured anterior spinal artery aneurysm is presented here. He experienced subarachnoid hemorrhage, which was confirmed by computed tomography. Magnetic resonance imaging revealed an aneurysm in front of the upper part of the medulla. Angiography demonstrated bilateral vertebral artery occlusion. Distal vertebral arteries and the basilar artery were perfused via the dilated anterior spinal artery, which originates in the right subclavian artery. The aneurysm was located at the distal part of the anterior spinal artery, and was successfully clipped through a lateral suboccipital craniotomy 2 months after bleeding from the aneurysm. After rehabilitation, the patient was able to walk with no apparent neurologic deficit. CONCLUSIONS: This case suggests that the anterior spinal artery as a collateral route after bilateral vertebral artery occlusion is under hemodynamic stress, resulting in aneurysm formation and rupture.
To determine whether actual numbers of human herpesvirus 6 (HHV-6) genome in hematologic neoplasias are associated with disease condition, we developed a quantitative PCR-ELISA for detection of HHV-6. The amount of viral DNA was determined using externally amplified known amounts of the plasmid DNA containing the viral target sequences. First, we determined a viral burden in peripheral blood leukocytes obtained from 23 healthy volunteers and four specimens of lymph nodes with reactive hyperplasia. Using 1 microg of DNA, the prevalence of HHV-6 was 43.4% (10/23), ranging from 0 to 100 HHV-6 genomes in blood obtained from healthy volunteers. The amounts of HHV-6 genomes were < 10 in four non-neoplastic lymph node specimens. We next examined the amount of viral DNA in 21 blood specimens and 19 lymph node specimens obtained from patients with lymphoproliferative diseases (LPD) at the time of diagnosis. The number of HHV-6 genomes in most of the B-cell lymphoma was < 5 in both blood and lymph node specimens, however, two lymph node specimens obtained from immunoblastic lymphadenopathy (IBL) and T-cell lymphoma had very high levels of HHV-6 viral DNA (3705 and 810, respectively). We also found that HHV-6 genomes in peripheral blood were more than 1000 in two patients with chronic lymphocytic leukemia. For all LPD patients combined, there were significantly higher levels of viral DNA (200.6 +/- 654.8 HHV-6 genomes per 1 microg purified DNA) compared to those in healthy volunteers (10.0 +/- 21.0 HHV-6 genomes per 1 microg purified DNA) (P < 0.05). This study demonstrates that a high level of HHV-6 viral DNA is occasionally associated with LPD patients. Although it is still uncertain whether HHV-6 is related to the pathogenesis in LPD or not, our results suggest that measurement of HHV-6 genomes using PCR-ELISA may be useful not only to understand the mechanism of HHV-6 infection in hemopoietic neoplasia but also to manage the care of immnocompromised patients such as bone marrow transplant patients.
A peptide with paralytic activity in larvae of the silkworm, Bombyx mori, was isolated from its hemolymph. Purification procedures consisted of extraction with 50% acetone, Vydac C4 reversed-phase cartridge elution and 4 steps of reversed-phase HPLC. Injection of the purified peptide into 4th instar B. mori larvae caused rapid and rigid paralysis for 2 min at a dose of 3.4 ng/larva. This paralytic peptide consists of 23 amino acid residues containing 2 cysteines with an intra-disulfide bond. The complete amino acid sequence is: H-Glu-AsnPhe-Val-Gly-Gly-Cys-Ala-Thr-Gly-Phe-Lys-Arg-Thr-Ala-Asp-G ly-Arg-Cys-Lys-Pro-Thr-Phe-OH. The relationship between structure and the biologic activity of synthetic analogs indicated that the entire amino acid sequence and the intra-disulfide bond were necessary for biological activity.
A linear peptide containing two reduced cysteine residues can be rapidly converted to its oxidized cyclic form containing an intramolecular disulfide bond by adding an excess of 2,2'-bispyridyl disulfide (2,2'-dipyridyl disulfide or 2,2'-dithiodipyridine) to conventional buffer solutions. The reactants and products are easily separated by reverse-phase chromatography. This reaction will find wide application in forming intramolecular disulfide bonds because of its selectivity for free sulfhydryl groups, quickness, safety, and applicability under acidic conditions.
Rice storage protein glutelin genes are coordinately regulated during seed development. A previous 5' deletion analysis using transgenic tobacco revealed that the minimum 5' region necessary for endosperm specificity was within -245 bp of the transcription start site, and included the AACA and GCN4 motifs that are highly conserved in the 5'-flanking regions of all glutelin genes. In this paper, the sequence elements essential for endosperm-specific expression are characterized in stable transgenic tobacco plants by both loss-of-function and gain-of-function experiments using this minimum promoter. Base substitution analysis shows that the proximal AACA motif between -73 and -61, and the GCN4 motif between -165 and -158 act as critical elements. An ACGT motif between -81 and -75, and Skn-I-like elements between -173 and -169 also play important roles in controlling the seed-specific expression. When the distal region between -245 and -145 containing the AACA and the GCN4 motifs or the proximal region between -113 and -46 containing the ACGT and AACA motifs is fused to a truncated promoter (-90 to +9) of the CaMV 35S gene fused to the beta-glucuronidase (GUS) reporter gene, high levels of seed-specific expression are observed in these fusions, thereby indicating that either pair of motifs is sufficient to confer seed expression in these fusions. However, when substituted for by the CaMV 35S core promoter (-46 to +1), seed expression is abolished, suggesting that the sequence between -90 and -46 of the CaMV 35S promoter containing G-box-like motif (as-1 element) is required for such specific expression in addition to AACA and GCN4 motifs. Therefore, we conclude that at least three cis-regulatory elements, the AACA motif, GCN4 motif and ACGT motif, are necessary to mediate endosperm expression of the GluB-1 glutelin gene.
The death receptor Fas transduces apoptotic death signaling upon stimulation with the Fas ligand. We previously reported that Fas contributes to vaginal cell death observed during the estrus cycle and after estrogen deprivation, using the functional Fas-lacking lpr and lprcg mutant mouse. In the present study, we investigated whether the Fas ligand also plays a dominant role in vaginal cell death using the functional Fas ligand-lacking gld mutant mouse. Our results demonstrated that vaginal cells of gld mice do not show any abnormalities, suggesting the possible presence of another ligand for Fas. Through our investigation, we demonstrated TNF-alpha as a ligand for vaginal Fas. Here, we propose that TNF-alpha acts for the ligand for Fas in vaginal cells, suggesting a new cell death induction system.